Biventricular pacing (BiVP) reverses intraventricular conduction delay (IVCD) and left ventricular (LV) dys- function in dilated cardiomyopathy (DCM). BiVP improves LV function and cardiac index (Cl) at no energy cost. The MIRACLE trial, in patients with DCM, IVCD and LV ejection fraction <35%, demonstrated improved subjective and objective measures of exercise tolerance and cardiac function with BiVP. BiVP benefits many, but selection criteria are not fully developed, and 30% of recipients are "nonresponders," at a cost of more than $2 billion/year. Preliminary data suggest that BiVP can benefit patients with low output states after cardiac surgery. We plan to assess surgical application of BiVP while assessing mechanisms of action and optimization. We will randomize 190 cardiac surgery patients with LV dysfunction preoperatively to paced and unpaced groups. BiVP will be optimized and continued postoperatively until patients are stable. BiVP will be assessed transiently in all patients at three time points. The primary end point is a 15% improvement in thermal dilution Cl measured in the intensive care unit (ICU). Effects of heart rate, atrioventricular delay, ventricular pacing site, and W timing on Cl will be assessed using a randomized sequence of data collection. Secondary end points include incidence of arrhythmias, inotropic support, urine output, weight gain, morbidity, mortality, and ICU costs. Related studies in three groups of 14 cardiac transplant recipients will assess BiVP effects on mechanics of in situ failing hearts with DCM or ischemic myopathy with or without inotropic support. The primary end point again is an increase in Cl, but each patient will undergo a randomized sequence of data collection for a 54-point matrix of six left ventricular pacing sites and nine W timings over 14 minutes, while measurements of Cl, contractility, intraventricular and interventricular synchrony and mitral regurgitation are recorded. Results will be displayed on two-dimensional response surfaces to define the best techniques for BiVP optimization. Patients with an increase in Cl < 20% will be assessed in detail to determine the etiology of failure to respond. These studies are important because of a high probability of clinical benefit. The methods employed will provide precision, breadth of measurement, and range of pacing sites superior to any other setting. The protocol will provide new and important scientific information that will benefit not only surgical patients but also the general population of BiVP recipients. [unreadable] [unreadable] [unreadable]